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Liposome Transport Protects Metabolic Activity of Prostate Cancer Drug

By LabMedica International staff writers
Posted on 30 Mar 2016
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Image: Structural model of the PAK1 protein (Photo courtesy of Wikimedia Commons).
Image: Structural model of the PAK1 protein (Photo courtesy of Wikimedia Commons).
The efficacy of liposome transport to protect the physiological activity of a small-molecule anti-prostate cancer drug was demonstrated both in vitro and in a mouse xenograft model.

The enzyme p21 protein (Cdc42/Rac)-activated kinase 1 (PAK1) has been implicated in various diseases including prostate cancer. It is one of a family of proteins encoded by the PAK1 gene. These proteins are critical effectors that link RhoGTPases to cytoskeleton reorganization and nuclear signaling, and they serve as targets for the small GTP binding proteins Cdc42 and Rac. This specific family member regulates cell motility and morphology.

The activity of PAK1 is inhibited by the small-molecular weight drug IPA-3 (inhibitor targeting PAK1 activation-3), which is highly specific but metabolically unstable. To overcome this limitation, investigators at the University of Georgia (Augusta, USA) encapsulated IPA-3 in sterically stabilized liposomes (SSL) that averaged 139 nanometers in diameter. Analysis of liposomal IPA-3 levels demonstrated good stability, with 70% of IPA-3 remaining after seven days.

The SSL-IPA-3 complex was used to treat prostate cancer cells growing in culture and mice with human prostate cancer xenografts. Results published in the March 3, 2016, online edition of the journal Nanomedicine: Nanotechnology, Biology and Medicine revealed that the drug inhibited prostate cancer cell growth in vitro with comparable efficacy to free IPA-3. Significantly, only a twice per week dose of SSL-IPA-3 was needed to inhibit the growth of prostate xenografts in vivo, while a similar dose of free IPA-3 was ineffective.

"PAK1 is kind of like an on/off switch," said senior author Dr. Somanath Shenoy, associate professor of pharmacology at the University of Georgia. "When it turns on, it makes cancerous cells turn into metastatic cells that spread throughout the body. When we first began these experiments, we injected IPA-3 directly into the bloodstream, but it was absorbed so quickly that we had to administer the treatment seven days a week for it to be effective. But the liposome that Dr. Cummings (University of Georgia) created makes the IPA-3 much more stable, and it reduced the treatment regimen to only twice a week. The results of our experiments are promising, and we hope to move toward clinical trials soon, but we must figure out what side effects this treatment may have before we can think about using it in humans."

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University of Georgia


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